Over 50 years of efforts, cellular reprogram- ruing opens a new door for disease modeling and regen- erative medicine. Although induction of pluripotency by transcription factors has become common, only a small portio...Over 50 years of efforts, cellular reprogram- ruing opens a new door for disease modeling and regen- erative medicine. Although induction of pluripotency by transcription factors has become common, only a small portion of basic mechanisms of epigenetic modifications during this process have been revealed. To clearly under- stand reprogramming and devise ways to promote full transition towards pluripotency, we must gain insight from comprehensive characterizations of cells at distinct repro- gramming stages, which involves gene expression profil- ing, chromatin state maps of key activating and repressive marks, and DNA modifications. Here, we review recent advances in epigenetic reprogramming to pluripotency with a focus on the principal molecular regulators and attach importance to the combination of high-throughput sequencing and systematic biology approaches in uncov- ering underlying molecular mechanisms of this unique platform in future researches.展开更多
Melanoma is the deadliest form of skin cancer with rising incidence and mortality rates. Although early-stage melanoma is highly curable, advanced-stage melanoma is refractory to treatment. This underscores the import...Melanoma is the deadliest form of skin cancer with rising incidence and mortality rates. Although early-stage melanoma is highly curable, advanced-stage melanoma is refractory to treatment. This underscores the importance of prevention and early detection as well as the need to improve treatment and prognostication of human melanoma. Elucidating the underlying mechanisms of the initi- ation and progression of human melanoma can help identify potential targets of intervention for prevention, diagnosis, therapy, and prognosis of this disease. Aberrant DNA methylation and histone modifications are the best-established epigenetic mechanisms of carcinogenesis. The occurrence of epigenetic changes prior to clinical diagnosis of cancer and their reversibility through pharmaco-logic/genetic approaches offer a promising avenue for basic and translational research on human melanoma. Candidate gene(s) or genome-wide aberrant DNA methylation and histone modifications have been observed in human melanoma tumor tissues and cell lines, and correlated to cellular and functional characteristics and/or clinicopathologicai features of this malignancy. The present review summarizes the published researches on aberrant DNA methylation and histone modifications in connection with human melanoma. Representative studies are highlighted to set forth the current state of knowledge, gaps in the knowledgebase, and future directions in these epigenetic fields of research. Examples of epigenetic therapy applied for human melanoma in vitro, and the challenges of its in vivo application for clinical treatment of solid tumors are discussed.展开更多
基金supported by the National Natural Science Foundation of China(31325019,91319306 and31401247)Ministry of Science and Technology of China(2015CB964800 and 2014CB964601)
文摘Over 50 years of efforts, cellular reprogram- ruing opens a new door for disease modeling and regen- erative medicine. Although induction of pluripotency by transcription factors has become common, only a small portion of basic mechanisms of epigenetic modifications during this process have been revealed. To clearly under- stand reprogramming and devise ways to promote full transition towards pluripotency, we must gain insight from comprehensive characterizations of cells at distinct repro- gramming stages, which involves gene expression profil- ing, chromatin state maps of key activating and repressive marks, and DNA modifications. Here, we review recent advances in epigenetic reprogramming to pluripotency with a focus on the principal molecular regulators and attach importance to the combination of high-throughput sequencing and systematic biology approaches in uncov- ering underlying molecular mechanisms of this unique platform in future researches.
文摘Melanoma is the deadliest form of skin cancer with rising incidence and mortality rates. Although early-stage melanoma is highly curable, advanced-stage melanoma is refractory to treatment. This underscores the importance of prevention and early detection as well as the need to improve treatment and prognostication of human melanoma. Elucidating the underlying mechanisms of the initi- ation and progression of human melanoma can help identify potential targets of intervention for prevention, diagnosis, therapy, and prognosis of this disease. Aberrant DNA methylation and histone modifications are the best-established epigenetic mechanisms of carcinogenesis. The occurrence of epigenetic changes prior to clinical diagnosis of cancer and their reversibility through pharmaco-logic/genetic approaches offer a promising avenue for basic and translational research on human melanoma. Candidate gene(s) or genome-wide aberrant DNA methylation and histone modifications have been observed in human melanoma tumor tissues and cell lines, and correlated to cellular and functional characteristics and/or clinicopathologicai features of this malignancy. The present review summarizes the published researches on aberrant DNA methylation and histone modifications in connection with human melanoma. Representative studies are highlighted to set forth the current state of knowledge, gaps in the knowledgebase, and future directions in these epigenetic fields of research. Examples of epigenetic therapy applied for human melanoma in vitro, and the challenges of its in vivo application for clinical treatment of solid tumors are discussed.